Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration
Cecília de Barros,
Norberto Aranha,
Patrícia Severino,
Eliana B. Souto,
Aleksandra Zielińska,
André Lopes,
Alessandra Rios,
Fernando Batain,
Kessi Crescencio,
Marco Chaud,
Thais Alves
Affiliations
Cecília de Barros
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Norberto Aranha
Technological and Environmental Processes, University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Patrícia Severino
Nanomedicine and Nanotechnology Laboratory (LNMed), Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju 49010-390, Sergipe, Brazil
Eliana B. Souto
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Ciências da Saúde, 3000-548 Coimbra, Portugal
Aleksandra Zielińska
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland
André Lopes
Faculty of Pharmaceutical Science, University of Campinas, Campinas 13083-871, São Paulo, Brazil
Alessandra Rios
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Fernando Batain
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Kessi Crescencio
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Marco Chaud
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
Thais Alves
Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, Brazil
The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.
